Observational Study of Neuromuscular Function in CMT Type 1&2 and Healthy Controls

Charcot-Marie-Tooth Disease Clinical Trial

— ESTABLISH  

Official title:

An Open Observational Study of Clinical and Electrophysiological Outcomes in Male and Female Patients With CMT Type 1 & 2, and Aged-matched Healthy Controls

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04980807
• Other study ID #: CMT Observational
• Status: Completed
• Start date: April 7, 2021
• Est. completion date: March 3, 2022

Study information

• Verified date: July 2021
• Source: NMD Pharma A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The primary aim of this study is to discover whether patients with CMT type 1 and 2 have neuromuscular junction transmission deficits.

The secondary aim is to collect information of different clinical and electrophysiological test procedures to perform possible future clinical trials in CMT patients.

Description:

The study is a prospective observational pilot study involving two investigational sites:

1. Department of Neurology, Arhus University Hospital

2. Department of Neurology, Ohio State University

A total of 20 patients with Charcot-Marie-Tooth (CMT) disease and 10 healthy age-matched controls will be included with each site including 10 CMT patients and 5 Healthy Controls. CMT patients will undergo electrophysiological (repetitive nerve stimulation and single fiber EMG analyses) and functional (different tests of muscle strength, fatigability, dexterity, and balance) testing on 4 separate occasions. Healthy controls will undergo electrophysiological testing at baseline only.

To assess whether patients with CMT have deficits in NMJ transmission, results from repetitive nerve stimulation and single fiber EMG analyses in CMT patients will be compared to those obtained in healthy controls at baseline. To inform future clinical trials, results relability and tolerability estimates obtained from sequential electrophysiological and functional tests will be calculated

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: March 3, 2022
• Est. primary completion date: March 3, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria for CMT Patients

• Age = 18 years

• Diagnosis of CMT confirmed by:

• Clinical presentation and electro diagnostics or genetics

• Physical Features (all must apply): 1) Ambulation for at least 10 meters, without a brace 2) Left and right ankle plantar flexion Medical Research Council (MRC) grade 2 to 5, inclusive 3) Left and right ankle dorsiflexion MRC manual muscle testing (MMT) grade 2 to 4+, inclusive.

• Ability to adhere to the study visit schedule/procedures, and to understand and comply with protocol requirements

• Stable concomitant medications for 2 months prior to enrolment

• Signed written informed consent

Exclusion Criteria for CMT Patients

• Severe deformity or ankle contracture that would sufficiently limit passive range of motion to affect assessment of dorsiflexion strength

• Ulceration that would interfere with functional ability

• Recent major surgery

• Significant change in physical activity or exercise (e.g., significant increase or decrease in intensity or frequency) within 8 weeks before Study Day 1 or inability to maintain the baseline level of physical activity throughout the study

• Any disability or condition that would prevent completion of the study tasks

• Moderate to severe Neuropathic or inflammatory/musculoskeletal pain that would interfere with performance of the tests

• A diagnosis of a primary NMJ disorder such as myasthenia gravis, Lambert Eaton Myasthenic Syndrome or congenital myasthenic disorder

Inclusion Criteria for Healthy Volunteers

• Healthy male or female volunteers

• Age =18 years

• Able to give written informed consent

Exclusion Criteria for Healthy Volunteers

• Pregnant

• Requiring prescription medicines likely to interfere with electromyography (EMG) recordings

• Presence of current or previous medical condition which might interfere with participation in the study

Related Conditions & MeSH terms

• Charcot-Marie-Tooth Disease
• Hereditary Sensory and Motor Neuropathy
• Nerve Compression Syndromes
• Tooth Diseases

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus	Jutland
United States	Ohio State University	Columbus	Ohio

Sponsors (3)

Lead Sponsor	Collaborator
NMD Pharma A/S	Aarhus University Hospital, Ohio State University

Countries where clinical trial is conducted

United States,  Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	CMTES2 Score	This test measures CMT disease severity. Total score is calculated as the sum of the 7 sub-scores with a maximum of score of 28	This test is performed at baseline in individuals with CMT disease
Other	Adverse Events	Number of adverse events by severity	At baseline for healthy controls and from baseline until final visit at day 42 for CMT patients
Other	Tolerability of test procedures	The tolerability score assessed on a 0-9 rating scale (0=no discomfort to 9=worst possible discomfort)	Performed for each test at each visit (baseline, day 14, 28 and 42)
Other	Association between NMJ function and clinical function in CMT patients	Correlation	Baseline
Primary	Repetitive Nerve Stimulation - difference between CMT patients and healthy controls	Percentage decrement of CMAP for the trapezius	Baseline
Primary	Repetitive Nerve Stimulation - difference between CMT patients and healthy controls	Percentage decrement of CMAP for abductor pollicis brevis	Baseline
Primary	Single Fiber Electro Myography (sfEMG) - difference between CMT patients and healthy controls	Percentage blocking	Baseline
Primary	Single Fiber Electro Myography (sfEMG) - difference between CMT patients and healthy controls	Jitter	Baseline
Secondary	Isometric Dynamometry - test reliability in patients with CMT	This test will be used to evaluate maximum isometric strength	The test is performed at baseline and day 14, 28 and 42.
Secondary	Manual Muscle Testing - test reliability in patients with CMT	This test is a physical examination of muscle strength. 15 muscle groups/motions will be tested. 13 of these are tested bilaterally. A total score between (0-280) is calculated	The test is performed at baseline and day 14, 28 and 42.
Secondary	9 Hole Peg Test - test reliability in patients with CMT	This is a test of finger dexterity	The test is performed at baseline and day 14, 28 and 42.
Secondary	6-Spot Step Test - test reliability in patients with CMT	This test is a quantitative measure of lower extremity function	The test is performed at baseline and day 14, 28 and 42.
Secondary	10-Meter Walk/run Test - test reliability in patients with CMT	This test measures how fast the participant can walk/run 10 meters.	The test is performed at baseline and day 14, 28 and 42.
Secondary	Timed Up and Go - test reliability in patients with CMT	This test measures how fast the participant can stand from a chair, walk 3 meters, turn around, return, and sit in the chair at a comfortable and safe pace	The test is performed at baseline and day 14, 28 and 42.
Secondary	Berg Balance Scale - test reliability in patients with CMT	The test measures balance during different functional tasks. A total score is calculated as the sum of the individual scores for each item, with maximum value 56, with a lower score meaning worse balance	The test is performed at baseline and day 14, 28 and 42.
Secondary	6 Minute Walk Test - test reliability in patients with CMT	This test measures how far a person can walk in six minutes	The test is performed at baseline and day 14, 28 and 42.
Secondary	Single Fiber Electro Myography (sfEMG) - test reliability in patients with CMT	Percantage blocking	The test is performed at baseline and day 14, 28 and 42.
Secondary	Single Fiber Electro Myography (sfEMG) - test reliability in patients with CMT	Jitter	The test is performed at baseline and day 14, 28 and 42.
Secondary	Repetitive Nerve Stimulation - test reliability in patients with CMT	Percentage decrement of CMAP for Trapezius	The test is performed at baseline and day 14, 28 and 42.
Secondary	Repetitive Nerve Stimulation - test reliability in patients with CMT	Percentage decrement of CMAP for abductor pollicis brevis	The test is performed at baseline and day 14, 28 and 42.